LDH-stabilized ultrasmall iron oxide nanoparticles as a platform for hyaluronidase-promoted MR imaging and chemotherapy of tumors

LDH-stabilized ultrasmall iron oxide nanoparticles as a platform for hyaluronidase-promoted MR imaging and chemotherapy of tumors
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LDH 稳定的超小氧化铁纳米粒子作为透明质酸酶促进的肿瘤 MR 成像和化疗的平台

DOI:
10.7150/thno.42906
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发表时间:
2020-02
期刊:
影响因子:
12.4
通讯作者:
Rui Guo
Rui Guo
中科院分区:
医学1区
文献类型:
--
作者:
Ni Zhang;Yue Wang;Changchang Zhang;Yu Fan;Du Li;Xueyan Cao;Jindong Xia;Xiangyang Shi;Rui Guo

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开发用于肿瘤成像和治疗的独特的治疗纳米平台仍然是当前纳米医学中的一个活跃话题。在这里,我们设计了一种新型的靶向治疗纳米平台,通过构建层状双氢氧化物(LDH)稳定的超小氧化铁(Fe3O4)纳米粒子(以透明质酸(HA)为靶向,高载药率的抗癌药物阿霉素(DOX)),用于增强T1加权磁共振(MR)成像引导化疗。方法:系统地表征了LDH-Fe3O4-HA/DOX纳米平台的结构和释药性能。以CD44受体高表达的B16黑色素瘤细胞为模型细胞,检测纳米平台的生物相容性、靶向性和治疗效果。体内实验采用透明质酸酶(HAASE)预处理和纳米平台给药相结合的方法,观察其磁共振成像和化疗效果。结果:LDH-Fe3O4-HA纳米杂化材料具有良好的胶体稳定性和细胞相容性,其R1弛豫度为原始超细Fe3O4的10倍(S 4.38 mm-1vs0.42 mm-1 S-1),并能以pH响应的方式释放药物。体外实验表明,LDH-Fe3O4-HA/DOX纳米杂化材料能够特异性地靶向高表达CD44受体的B16细胞,并有效地将DOX释放到细胞核。体内实验结果表明,通过HAase对肿瘤组织进行预处理以降解细胞外基质中过表达的HA,所设计的纳米平台具有更好的肿瘤穿透性,可显著增强肿瘤的磁共振成像,并以较低的副作用进行肿瘤化疗。结论:所设计的LDH-Fe3O4-HA/DOX纳米杂化材料有望成为CD44受体高表达肿瘤增强T1加权磁共振引导化疗的新型靶向治疗纳米平台。
Development of unique theranostic nanoplatforms for tumor imaging and therapy remains an active topic in current nanomedicine. Here, we designed a novel targeted theranostic nanoplatform for enhanced T1-weighted magnetic resonance (MR) imaging-guided chemotherapy by constructing layered double hydroxide (LDH)-stabilized ultrasmall iron oxide (Fe3O4) nanoparticles with hyaluronic acid (HA) modified as targeting agents, and anticancer drug doxorubicin (DOX) loaded with a high loading efficiency. Methods: The structure and release property of LDH-Fe3O4-HA/DOX nanoplatforms were characterized systematically. B16 melanoma cells with CD44 receptors overexpressed were used as model cells to determine the biocompatibility, targeting capability, and therapeutic efficiency of nanoplatforms. For in vivo experiment, hyaluronidase (HAase) pretreatment was combined with nanoplatform administration to investigate the MR imaging and chemotherapeutic effect. Results: The LDH-Fe3O4-HA nanohybrids possess good colloidal stability and cytocompatibility, display an r1 relaxivity 10-fold higher than the pristine ultrasmall Fe3O4 (4.38 mM-1 s-1 vs 0.42 mM-1 s-1), and could release drug in a pH-responsive manner. In vitro experiments demonstrate that LDH-Fe3O4-HA/DOX nanohybrids are able to specifically target B16 cells overexpressing CD44 receptors and effectively release DOX to nucleus. In vivo results show that with the pretreatment of tumor tissue by HAase to degrade the overexpressed HA in extra-cellular matrix, the designed nanoplatforms have a better tumor penetration for significantly enhanced MR imaging of tumors and tumor chemotherapy with low side effects. Conclusion: The designed LDH-Fe3O4-HA/DOX nanohybrids may be developed as a novel targeted theranostic nanoplatform for enhanced T1-weighted MR imaging-guided chemotherapy of CD44 receptor-overexpressing tumors.
DOI: 10.1016/j.biomaterials.2013.01.077
发表时间: 2013-04
期刊: BIOMATERIALS
影响因子: 14
作者:
Ganesh, Shanthi;Iyer, Arun K.;Morrissey, David V.;Amiji, Mansoor M.
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发表时间: 2018
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发表时间: 2018-12
影响因子: 9.9
作者:
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锰基磁性层状双氢氧化物纳米粒子:一种pH敏感且同时增强的T-1/T-2加权双模磁共振成像造影剂
DOI: 10.1021/acsbiomaterials.8b01618
发表时间: 2019
影响因子: --
作者:
Xie Wensheng;Guo Zhenhu;Cao Zhenbang;Gao Qin;Wang Dan;Boyer Cyrille;Kavallaris Maria;Sun Xiaodan;Wang Xiumei;Zhao Lingyun;Gu Zi
通讯作者: Gu Zi
DOI: 10.1039/c8cc09185d
发表时间: 2019-02
影响因子: 4.9
作者:
Yu Luo;Yan Tang;Tianzhi Liu;Qian Chen;Xiaohan Zhou;Ning Wang;Ming Ma;Yingsheng Cheng;Hangrong Chen
通讯作者: Yu Luo;Yan Tang;Tianzhi Liu;Qian Chen;Xiaohan Zhou;Ning Wang;Ming Ma;Yingsheng Cheng;Hangrong Chen